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A bacterial autotransporter impairs innate immune responses by targeting the transcription factor TFE3

Author

Listed:
  • Atri Ta

    (UConn Health School of Medicine)

  • Rafael Ricci-Azevedo

    (UConn Health School of Medicine)

  • Swathy O. Vasudevan

    (UConn Health School of Medicine)

  • Skylar S. Wright

    (UConn Health School of Medicine)

  • Puja Kumari

    (UConn Health School of Medicine)

  • Morena S. Havira

    (Arvinas, Inc.)

  • Meera Surendran Nair

    (Pennsylvania State University)

  • Vijay A. Rathinam

    (UConn Health School of Medicine)

  • Sivapriya Kailasan Vanaja

    (UConn Health School of Medicine)

Abstract

Type I interferons (IFNs) are consequential cytokines in antibacterial defense. Whether and how bacterial pathogens inhibit innate immune receptor-driven type I IFN expression remains mostly unknown. By screening a library of enterohemorrhagic Escherichia coli (EHEC) mutants, we uncovered EhaF, an uncharacterized protein, as an inhibitor of innate immune responses including IFNs. Further analyses identified EhaF as a secreted autotransporter—a type of bacterial secretion system with no known innate immune-modulatory function—that translocates into host cell cytosol and inhibit IFN response to EHEC. Mechanistically, EhaF interacts with and inhibits the MiT/TFE family transcription factor TFE3 resulting in impaired TANK phosphorylation and consequently, reduced IRF3 activation and type I IFN expression. Notably, EhaF-mediated innate immune suppression promotes EHEC colonization and pathogenesis in vivo. Overall, this study has uncovered a previously unknown autotransporter-based bacterial strategy that targets a specific transcription factor to subvert innate host defense.

Suggested Citation

  • Atri Ta & Rafael Ricci-Azevedo & Swathy O. Vasudevan & Skylar S. Wright & Puja Kumari & Morena S. Havira & Meera Surendran Nair & Vijay A. Rathinam & Sivapriya Kailasan Vanaja, 2023. "A bacterial autotransporter impairs innate immune responses by targeting the transcription factor TFE3," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37812-2
    DOI: 10.1038/s41467-023-37812-2
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    1. Nicole T. Perna & Guy Plunkett & Valerie Burland & Bob Mau & Jeremy D. Glasner & Debra J. Rose & George F. Mayhew & Peter S. Evans & Jason Gregor & Heather A. Kirkpatrick & György Pósfai & Jeremiah Ha, 2001. "Genome sequence of enterohaemorrhagic Escherichia coli O157:H7," Nature, Nature, vol. 409(6819), pages 529-533, January.
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